MGD009/MGA012 Combination in Relapsed/Refractory Cancer

This study is a Phase 1, open-label, dose escalation, and cohort expansion study designed to
characterize the safety, tolerability, PK, pharmacodynamics, immunogenicity, and preliminary
antitumor activity of the combination of MGD009 and MGA012, each of which is administered by
IV infusion.The study consists of a Dose Escalation Phase to determine the Maximum Tolerated
Dose (MTD) or Maximum Administered Dose (MAD) (if no MTD is defined) of the combination,
followed by a Cohort Expansion Phase to further define the safety and initial antitumor
activity of the combination with the doses established in the Dose Escalation Phase. Patients
with B7-H3-expressing unresectable, locally advanced, or metastatic solid tumors of any
histology will be enrolled in the Dose Escalation Phase. Following the establishment of an
MTD, additional patients with specific tumor types will enroll in the Cohort Expansion Phase.

Inclusion Criteria:

- Histologically-proven, unresectable locally advanced or metastatic solid tumors of any
histology that test positive for B7-H3 expression on tumor cells or vasculature for
whom no approved therapy with demonstrated clinical benefit is available. For all
tumor types, the requirement for previous systemic therapy may be waived if a patient
was intolerant of or refused standard first-line therapy

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Life expectancy ≥ 12 weeks

- Measurable disease, with the exception of prostate cancer

- Tissue specimen available for B7-H3 and PD-L1 expression testing

- Acceptable laboratory parameters

- Patients who have previously received an immune checkpoint inhibitor (e.g., anti-
PD-L1, anti-PD-1, anti-CTLA-4) prior to enrollment must have toxicities related to the
checkpoint inhibitor resolved to ≤ Grade 1 or baseline (prior to the checkpoint
inhibitor) to be eligible for enrollment. Patients who experienced previous
hypothyroidism toxicity on a checkpoint inhibitor are eligible to enter study
regardless of Grade resolution as long as the patient is well controlled on thyroid
replacement hormones.

Exclusion Criteria:

- Patients with history of prior central nervous system (CNS) metastasis must have been
treated, must be asymptomatic, and must not have any of the following at the time of
enrollment:

1. No concurrent treatment for the CNS disease (e.g. surgery, radiation,
corticosteroids >10 mg prednisone/day or equivalent)

2. No progression of CNS metastases on MRI or CT for at least 14 days after last day
of prior therapy for the CNS metastases

3. No concurrent leptomeningeal disease or cord compression

- Patients with any history of known or suspected autoimmune disease with the specific
exceptions of vitiligo, resolved childhood atopic dermatitis, psoriasis not requiring
systemic treatment (within the past 2 years), and patients with a history of Grave's
disease that are now euthyroid clinically and by laboratory testing

- Treatment with any, investigational therapy within the 4 weeks prior to the initiation
of study drug administration

- Treatment with any systemic chemotherapy within 3 weeks

- Treatment with radiation therapy within 2 weeks

- History of allogeneic bone marrow, stem-cell, or solid organ transplant

- Treatment with systemic corticosteroids (> 10 mg per day prednisone or equivalent) or
other immune suppressive drugs within 2 weeks

- Clinically significant cardiovascular or pulmonary disease

- Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral
treatment within 7 days prior to the initiation of study drug. Patients requiring any
systemic antiviral, antifungal, or antibacterial therapy for active infection must
have completed treatment no less than one week prior to the initiation of study drug.

- Known history of positive testing for human immunodeficiency virus or history of
acquired immune deficiency syndrome

- Known history of hepatitis B or hepatitis C infection or known positive test for
hepatitis B surface antigen, hepatitis B core antigen, or hepatitis C polymerase chain
reaction